MFR of Levocetirizine 5 mg Tablets IP
TABLE OF CONTENTS
| S.NO. | TITLE | Page No. | |
| 1.0 | PRODUCT DETAILS | ||
| 2.0 | MANUFACTURING FORMULA | ||
| 3.0 | LIST OF EQUIPMENTS | ||
| 4.0 | GENERAL PRECAUTIONS | ||
| 5.0 | MANUFACTURING INSTRUCTIONS | ||
| 6.0
|
MANUFACTURING PROCESS DETAILS | ||
| 6.1 | GRANULATION | ||
| 6.2 | COMPRESSION | ||
| 6.3 | COATING | ||
| 6.4 | BRAND DETAILS | ||
1.0 PRODUCT DETAILS:
| Product Name | Levocetirizine Dihydrochloride Tablets IP |
| Product Description | White color round shape, biconvex, film coated tablet having both side plain. |
| Strength | 5 mg |
| Label claim
|
Each film coated tablet contains:
Levocetirizine Dihydrochloride IP – 5 mg |
| Batch Size | 5,00,000 Tablets |
| Average Weight | 100 mg (Uncoated tablets)
102 mg (Film coated tablets) |
| Shelf Life | 24 months |
| Storage | Store in a cool, dry and dark place below 25 0C |
| Drug Category | Anti-histamine Drug |
2.0 MANUFACTURING FORMULA:
| Material Name | Grade | Category | Quantity per Unit (In mg) | Overages | Batch Qty.
(In kg) |
|
| Dry Mixing | ||||||
| Levocetirizine Dihydrochloride | IP | API | 5 mg | 1 % | 2.525 kg | |
| MCCP PH-102 | IP | Diluent | 10.15 mg | — | 5.075 kg | |
| Starch | IP | Diluent | 5.0 mg | — | 2.500 kg | |
| Cross Carmillose Sodium | IP | Disintegrants | 1.25 mg | — | 0.625 kg | |
| Binder | ||||||
| Ethyl Cellulose | IP | Binder | 0.02 mg | — | 0.010 kg | |
| Isopropyl Alcohol (IPA) | IP | Solvent | 0.02 ml | — | 10.800 liter | |
| Lubricant | ||||||
| Talcum | IP | Anti-caking agent | 3 .0 mg | — | 1.500 kg | |
| MCCP PH-102 | IP | Diluent | 71.30 mg | — | 35.650 kg | |
| Cross Carmillose Sodium | IP | Disintegrants | 1.25 mg | — | 0.625 kg | |
| Aerosil | IP | Glidant | 1.0 mg | — | 0.500 kg | |
| Calcium Stearate | IP | Anti-Adherent | 2.0 mg | — | 1.000 kg | |
3.0 LIST OF EQUIPMENTS:
| Sr. No. | Machineries/Equipments | Capacity | Equipment ID. |
| 1. | Weighing Balance | 100 kg | |
| 2. | Vibro Sifter (with SS Sieves No’s 14,40,60 and 100) | 30 inch dia | |
| 3. | Mass Mixer with propeller | 100 liter | |
| 4. | Portable Stirrer | — | |
| 5. | Tray Dryer | 48 Trays | |
| 6. | Double Cone Blender | 200 liter | |
| 7. | Halogen Moisture Balance | — | |
| 8. | Compression Machine | 35 Station | |
| 9. | SS Containers with lid | 20 liter (02 No’s) | — |
| 10. | Poly-lined HDPE Containers with lid | 30 liter (05 No’s) | — |
| 11. | Polybags | 2.0 ,20 and 50 kg | |
| 12. | Filter Cloth 100 # | 0.5 meter |
4.0 GENERAL PRECAUTIONS:
- API Description: A white or almost white powder.
- All the Manufacturing Activities shall be performed under controlled conditions (temperature NMT 25 0C and relative humidity NMT 60%).
- When working with Active Ingredients and drug product or mixture of Active Ingredients and Excipients, wear gloves and mask to avoid exposure and contact with any body parts.
5.0 MANUFACTURING INSTRUCTIONS:
- All activities shall be performed as per current SOPs.
- Take the line clearance from QA before starting the manufacturing operation during batch to batch and product to product change over.
- Do not overwrite any entry. In case of mistake, cancel the entry by single line with sign & date and make correct entry.
- MANUFACTURING PROCESS DETAILS:
6.1 GRANULATION:
STEP – I (SIFTING):
- Check Sieve Integrity (before sifting and after sifting).
- Set the Vibro Sifter (capacity: 30 inch dia) and sieve the Dispensed Materials as per Sieve Sizes mentioned below:
| Material Name | Std. Qty. (kg) | Sieve No. |
| Dry Mixing | ||
| Levocetirizine Dihydrochloride IP | 2.525 kg | 40 # |
| MCCP PH-102 IP | 5.075 kg | 40 # |
| Starch IP | 2.500 kg | 100 # |
| Cross Carmillose Sodium IP | 0.625 kg | 40 # |
| Binder | ||
| Ethyl Cellulose IP | 0.010 kg | — |
| Isopropyl Alcohol IP ( IPA) | 10.800 liter | — |
| Lubricant | ||
| Talcum IP | 1.500 kg | 60 # |
| MCCP PH-102 IP | 35.650 kg | 40 # |
| Cross Carmillose Sodium IP | 0.625 kg | 40 # |
| Aerosil IP | 0.500 kg | 14 # |
| Calcium Stearate IP | 1.000 kg | 60 # |
- Collect the sifted Levocetirizine Dihydrochloride IP (2.525 kg), MCCP PH-102 IP (5.075 kg), Starch IP (2.500 kg) and Cross Carmillose Sodium IP (0.625 kg) in one Polybag (capacity: 20 kg).
- Collect the sifted Talcum IP (1.500 kg), MCCP PH-102 IP (35.650 kg), Cross Carmillose Sodium IP (0.625 kg) and Aerosil IP (0.500 kg) in one Polybag (capacity: 50 kg).
- Collect the sifted Calcium Stearate IP (1.000 kg) in one Polybag (capacity: 2.0 kg).
STEP – II (BINDER PREPARATION):
Take Isopropyl Alcohol IP (10.800 liter) in SS Container (capacity: 20 liter) and add Ethyl Cellulose IP (0.010 kg) in it. Mix together by Portable Stirrer continuously stirring till Ethyl Cellulose IP is dissolved properly in IPA.
Mixing Time: 10 minutes.
Filter it with filter cloth 100 # in SS container (capacity: 20 liter).
STEP – III (DRY MIXING):
Transfer the sifted material Levocetirizine Dihydrochloride IP, MCCP PH-102 IP, Starch IP and Cross Carmillose Sodium IP in Mass Mixer ( capacity : 100 liter) and dry mix the materials till uniform mixing.
Mixing Time: 10 minutes.
Mixing Speed: 36 RPM
Paddle (Blades) Timing: 5 minutes in clockwise direction and 5 minutes in anti-clockwise direction.
STEP –IV (BINDING OF DRY MIX MATERIAL):
Slowly add the binder of Step-II in dry mix material of Step-III and mix for 10 minutes till uniform binding and after binding, collect the wet mass in four Trays (capacity: 3.000 kg each).
Mixing Time: 10 minutes.
Mixing Speed: 36 RPM.
Paddle (Blades) Timing: 5 minutes in clockwise direction and 5 minutes in anti-clockwise direction.
STEP –V (DRYING):
Dry the wet material of Step-IV as follows:
Load these four Trays in Tray dryer.
First air dry the granules for 30 minutes in Tray Dryer. Ensure that Heaters are in OFF mode during air drying. After 30 minutes of air drying Switch ON the heaters and set the temperature at 35°C and dry the granules, until the LOD of granules is achieved between 1.0 to 1.5 % at 105°C checking by Halogen Moisture Balance.
Drying Temperature: 35°C (After Air Drying)
Drying Time: 03 hours (To be validated in next batch).
Raking Frequency: After every 20 minutes.
STEP-VI (SIZING/MILLING):
Check Sieve Integrity (before sifting and after sifting).
Set the Vibro Sifter and fix the sieve 40 # and sieve the dried material of Step-V. Collect the sized granules in one Poly-lined HDPE Container (capacity: 30 liter).
STEP – VII (PRE –LUBRICATION):
Load the sized granules of Step-VI in Double Cone Blender (capacity : 200 liter) and add sifted Talcum IP, MCCP PH-102 IP, Cross Carmillose Sodium IP and Aerosil IP, mix properly till uniform mixing of sized material with Pre-Lubricating Materials.
Mixing Time: 40 minutes (20 minutes clockwise direction and 20 minutes anti-clockwise direction).
Mixing Speed: 10 RPM.
STEP – VIII (LUBRICATION):
Add the sifted Calcium Stearate IP in Pre- Lubricated Materials of Step-VII in Double Cone Blender and mix properly till uniform mixing of materials with Calcium Stearate IP.
Mixing Time: 05 minutes (clockwise direction).
Mixing Speed: 10 RPM.
STEP- IX (BLEND SAMPLE ANALYSIS):
After completion of lubrication, collect the composite blend sample (Qty: 10 gm) and send to QC for analysis according to the table below:
| Test | Specification |
| Appearance of blend
Blend Uniformity Blend Assay LOD Bulk Density Tapped Density Compressibility Index Hausner Ratio |
White free flowing granular powder
90 % to 110 % 98 % to 103 % 1.0 % to 1.5 % To be established in next batch To be established in next batch To be established in next batch To be established in next batch |
STEP – X:
- Take Tare Weight of two Poly-lined HDPE Containers (capacity: 30 liter each), record the Tare Weight in BMR and unload the above blended material from Double Cone Blender in Poly-lined HDPE Containers (capacity: 30 liter each) and weigh the material with containers and record the Gross Weight of the material and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
- Batch Yield of Lubricated granules:
Theoretical Batch Yield: 50.000 kg (100 %)
Actual Batch Yield Limit: 49.500 kg (NLT 99 %) (To be established in next batch).
STEP – XI:
- Clean all equipments used in the granulation as per respective equipment cleaning SOP.
6.2 COMPRESSION:
STEP – I:
- After receiving of QC approval for the blend, verify the Net Weight of the received blend as per status label in Granules Day Store.
- Set the 35 stations (B-Tooling) Compression Machine. Compress the blend as per below parameters and In Process checks and take a sample for Dissolution (Qty. 20 tablets) and send to QC Department for Dissolution Analysis.
- After confirmation of Dissolution result continue the compression with the blend as per the following parameters and In Process checks under controlled environmental condition.
| S.No. | Parameters | Standard | No. of Tablets | In-Process Frequency |
| 1. | Feed frame alignment and adjustment | Should be satisfactory | —– | —– |
| 2. | Lower Weight Assembly | Should be satisfactory | —– | —– |
| 3. | Hydraulic Pressure | 5-6 Tones | —– | —– |
| 4. | Machine Speed | 18 RPM to 22 RPM | —– | —– |
| 5. | Upper Punch Size | 6.5 mm | —– | —– |
| 6. | Lower Punch Size | 6.5 mm | —– | —– |
| 7. | Die | 6.5 mm | —– | —– |
| 8. | Diameter | 6.5 mm | 6/Individual | 2 hours |
| 9. | Thickness of Tablets | 2.5 mm ± 0.2 mm | 6/Individual | 2 hours |
| 10. | Weight of 20 Tablets | 2.00 gm ± 2 % | 20/Composite | 30 minutes |
| 11. | Tablets for Dissolution | 100 mg ± 2 % | 20/ Composite | Before starting the Compression |
| 12. | Dissolution | NLT 80 % | —- | —- |
| 13. | Product Description | White color, round shape, biconvex, uncoated tablet having both side plain. | 20/Composite | 30 minutes |
| 14. | Uniformity of Weight | NMT 02 tablets out of 20 deviate from the standard average weight by more than 3 % and no single tablet deviates from the standard average weight by more than 5 % | 20/Composite | 01 hour |
| 15. | Standard Average Weight of Tablets | 100 mg ± 2 % | 20/Individual | 30 minutes |
| 16. | Hardness | NLT 3.0 kg/cm2 | 6/Individual | 30 minutes |
| 17. | Disintegration Time | NMT 15 min (IHS NLT 03 minute) | 6/Composite | 01 hour |
| 18. | Friability | NMT 1% | 20/Composite | 01 hour |
- Collect the compressed tablets in SS Container (capacity: 20 liter each on both sides), when SS containers are filled with tablets, transfer the tablets in two Poly-lined HDPE Containers as given in below Step-III.
STEP – II:
- Send the sample of compressed tablets (Qty. 30 tablets) to QC department for analysis.
STEP – III:
- Take Tare Weight of two Poly-lined HDPE Containers (capacity: 30 liter each), record the Tare Weight in BMR and transfer the compressed tablets in Poly-lined HDPE Containers (capacity: 30 liter each) and weigh the compressed tablets with containers and record the Gross Weight of the compressed tablets and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Avg. Weight, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
- Batch Yield of Compressed Tablets:
Theoretical Batch Yield: 50.000 kg (100 %).
Actual Batch Yield Limit: 49.500 kg (NLT 99 %) (To be established in next batch).
STEP – IV:
- After completion of compression of tablets, clean the Compression Machine as per cleaning SOP.
6.3 COATING:
- Verify the Net Weight of the received compressed tablets for coating as per status label and after confirmation continue for tablet coating.
STEP – I (COATING MATERIALS DETAILS):
| S. No. | Material Name | Batch Quantity |
| 1. | Instacoat White Aq.III | 1.000 kg. |
| 2. | Purified Water IP | 6.000 liter |
NOTE:
STEP-II (LIST OF EQUIPMENTS FOR COATING):
| Sr. No. | Machineries/Equipments | Capacity | Equipment ID. |
| 1. | Coating Machine and Coating Pan | 36″ | |
| 2. | Spray Gun | 01 | — |
| 3. | Filter Cloth 100 # | 0.5 meter | — |
| 4. | Portable Stirrer | — | — |
| 5. | SS Container | 10 liter (02 No’s) | — |
| 6. | Poly-lined HDPE Containers with lid | 30 liter (02 No’s) | — |
STEP – III (PREPARATION OF COATING SOLUTION):
- Take Purified Water IP (6.000 liter at room temperature) in SS Container (capacity: 10 liter) and add Instacoat White Aq.III (1.000 kg) and mix together by Portable Stirrer continuously stirring till uniform mixing achieved.
Speed of Stirrer: Constant.
Mixing Time: 15 minutes.
- Filter the coating solution with Filter Cloth 100 # in SS Container (capacity: 10 liter).
- Keep the solution for 15 minutes to let it the foam settle down. Thereafter proceed with coating process.
STEP – IV (COATING PROCEDURE):
- Coating will be done in one lot, take total compressed tablets for coating (50.000 kg).
- Load the tablets in coating pan (Capacity: 36″), start the hot air blower, set the inlet air temperature at 60°C to 65°C and start the exhaust fan & warm the tablets bed 40°C to 45°C.
- After warming up the tablets, take weight of 100 warmed tablets and record the weight in BMR for calculation of weight buildup of tablets after coating.
- Set the coating parameter as given in below table and start the coating process by starting coating spray through gun.
| Parameter | Specification |
| No. of Baffles in coating pan | 03 |
| No. of Guns | 01 |
| Inlet Temperature | 60°C to 65°C (To be validated in next batch) |
| Peristaltic Pump Speed | 2 – 4 RPM (To be validated in next batch) |
| Atomization | 2.5 to 3.0 kg/cm2 |
| Gun to Tablet Bed Distance | 10 inch |
| BED Temperature | 400C to 45 0C (To be validated in next batch) |
| Pan RPM | 13 to 15 RPM |
| % Weight Gain | 1.5 to 2.0 % |
| Coating Time | 01 Hour (To be validated in next batch) |
STEP – V (COATING IN-PROCESS CHECK PARAMETERS):
| S.No. | Parameters | Standard | No. of Tablets | In-Process Frequency |
| 1 | Product Description | White color, round shape, biconvex, film coated tablet having both side plain | 20 No. |
After batch completion |
| 2 | Weight of 20 Tablets after coating | 2.040 gm. ± 2 % | 20 No. | |
| 3 | Standard Average Weight after coating | 102 ± 2 % | 20 No. | |
| 4 | Individual Tablets Weight Variation | NMT 02 tablets out of 20 deviate from the standard average weight by more than 3 % and no single tablet deviates from the standard average weight by more than 5 % | 20 No. | |
| 5 | Thickness | 2.6 mm ± 0.2 mm | 6 No. | |
| 6 | Disintegration | NMT 30 min. | 6 No. |
STEP – VI:
- Send the composite sample of coated tablets (Qty. 30 tablets) to QC department for analysis.
STEP – VII:
- Take Tare Weight of two Poly-lined HDPE Containers (capacity: 30 liter each), record the Tare Weight in BMR and transfer the coated tablets in Poly-lined HDPE Containers (capacity: 30 liter each) and weigh the coated tablets with containers and record the Gross Weight of the coated tablets and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
- Affix the status label with following details – Product Name, Batch No., Batch Size, Avg. Weight, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
- Batch Yield of Coated Tablets:
Theoretical Batch Yield: 51.000 kg (100 %)
Actual Batch Yield Limit NLT 50.490 kg (NLT 99 %) (To be established in next batch).